On December 5, Alina Iovleva, first year ID fellow, presented an article on a challenging topic- vertebral osteomyelitis.  The article was a single center retrospective cohort regarding step down therapy after 2 weeks of intravenous antibiotics.   The study is from 2014 an was performed by Babouee Flury and colleagues and published in BMC infectious diseases.   The study included 10 year review of patients, and excluded those who had spinal hardware, endocarditis, post-operative infections, and those lost to follow-up.

Overall 68 patients were included 21% with Staph aureus, 17% coagulase negative staph, 20% streptococci. Overall Gram negatives made up 28% of the infections.    All patients were started on intravenous antibiotics, and 66% were changed to oral antibiotics by 14 days and 72% by 19 days. Retrospectively, a larger C reactive protein drop at 2 weeks from diagnosis predicted change to oral.  Other than patients who died  from malignancy the patients did well and  the remaining  patient were all cured at 1 year.  Those lost to follow-up were excluded so this confounds the overall success rate with selection bias/availability bias.

The bulk of the discussion at this journal club focused on the antibiotic choices. While the distribution of antibiotics were given in the data, there was no “bug-drug” matched table to compare specific regimens for each pathogen.  The majority of patients (74%) received a quinolone in monotherapy or combination therapy.  According the guidelines form 2015 from the IDSA , oral quinolone therapy is one of the oral options for gram negative pathogens.  The data for oral quinolones (if taken correctly separated from divalent cations) goes back nearly  30 years  but as a class they are not recommended for staphylococcal infections as monotherapy.   There is a recommendation for alternative therapy for levofloxacin + rifampin OR moxifloxacin + rifampin for staphylococcal infections.  In addition, oral clindamycin is a second line agent for staphylococcal vertebral osteomyelitis, when susceptible.

Additionally , there is the question of quinolone resistance in an age of MRSA is of note.  The rate of MRSA in Switzerland where the study was conducted is low, but the rate of MRSA in the study was not reported.  Often MRSA isolates have lower quinolone susceptibility and can have RIF resistance, which may make FQ/RIF strategy less appealing.

Overall there is some hesitancy to use oral therapy for gram-positive vertebral osteomyelitis – especially Staphylococcus aureus.  While IV therapy with high dose beta-lactam comes with its own risks (PICC line infection, allergic reactions), clindamycin (C. diff), quinolones (C. diff, QTc prolongation, tendon rupture) + rifampin (hepatotoxicity), linezolid (cytopenias, lactic acidosis) are not without risk even if they avoid a PICC line.  There is no robust data for doxycycline as primary treatment for osteomyelitis in this setting.   Lastly, there is randomized trial data that Bactrim + rifampin is as good an IV anti-staphylcoccal pencillin for chronic (diabetic) osteomyelitis (after debridement), but this has not been established for acute vertebral osteomyelitis.  ( .

In the future, we may have preliminary data on the long acting anti-gram positive drugs (oritavancin/dalbavancin) in the setting of bone/joint infections.  If these are promising, patients may be able to be treated with 4 (or fewer) doses of these medications at 1-2 week intervals and would preclude the need for picc or an oral alternative in many cases.It would be ideal to determine which patients still require IV therapy for this severe infection, and which factors would suggest success via a step-down or all-oral strategy.

[JAV]

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Pubmed:

Babouee Flury B Et al.  Is switching to an oral antibiotic regimen safe after 2 weeks of intravenous treatment for primary bacterial vertebral osteomyelitis? BMC Infect Dis. 2014 Apr 27;

Brebari EF et al 2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults. Clin Infect Dis. 2015 Sep 15;61(6):e26-46.

Greenberg RN et al, Randomized trial of ciprofloxacin compared with other antimicrobial therapy in the treatment of osteomyelitis. Am J Med. 1987 Apr 27;82(4A):266-9.

Euba G et al Long-term follow-up trial of oral rifampin-cotrimoxazole combination versus intravenous cloxacillin in treatment of chronic staphylococcal osteomyelitis. Antimicrob Agents Chemother. 2009 Jun;53(6):2672-6.